2. Academic Validation
  3. Improvement of the Intestinal Absorption of Dihydroquercetin (DHQ) by Flavonoids via Inhibiting P-Glycoprotein (P-gp)-Mediated Efflux in P-gp Overexpressed KB/MDR1 Cells and Caco-2 Monolayers

Improvement of the Intestinal Absorption of Dihydroquercetin (DHQ) by Flavonoids via Inhibiting P-Glycoprotein (P-gp)-Mediated Efflux in P-gp Overexpressed KB/MDR1 Cells and Caco-2 Monolayers

  • J Agric Food Chem. 2026 Feb 11;74(5):4823-4836. doi: 10.1021/acs.jafc.5c12044.
Hainan Song 1 2,  Weiwei Cao 3,  Xiushi Chen 1 2,  Siqi Peng 1 2,  Wenlong Sun 1 2,  Xiaojun Yang 1 2,  Mahmoud Salah 4,  Mohamed A Farag 5,  Yajing Fang 1 2
Affiliations

Affiliations

  • 1 School of Food Science and Engineering, Key Laboratory of Food Nutrition and Functional Food of Hainan Province, Hainan University, Haikou 570228, China.
  • 2 Collaborative Innovation Center of One Health, Hainan University, Haikou 570228, China.
  • 3 College of Food and Bioengineering, Henan University of Science and Technology, Luoyang 471023, China.
  • 4 Mahmoud Salah Department of Environmental Agricultural Science, Faculty of Graduate Studies and Environmental Research, Ain Shams University, Cairo 11566, Egypt.
  • 5 Pharmacognosy Department, College of Pharmacy, Cairo University, Cairo, Kasr El Aini St., PB 11562, Egypt.
PMID: 41592218 DOI: 10.1021/acs.jafc.5c12044
Abstract

Effects of four flavonoid inhibitors (FIs, quercetin, kaempferol, luteolin, and flavone) at different concentrations on dynamically increasing dihydroquercetin (DHQ) uptakes and regulating P-glycoprotein (P-gp)'s mRNA and protein levels were evaluated in KB/MDR1 cells. DHQ's bidirectional transport was measured in Caco-2 monolayers. The low uptakes of DHQ were dynamically increased by four FIs (better than elacridar) in the order of quercetin > luteolin > kaempferol > flavone. Four FIs significantly increased DHQ40's uptakes in a dose-independent manner. Four FIs alone or with DHQ significantly decreased P-gp's mRNA and protein expressions. DHQ was poorly absorbed (efflux ratios >20) in Caco-2 monolayers, especially at high concentrations. Four FIs improved DHQ's absorption by significantly increasing (reversing) its influx (efflux) at most time points (1, 2, 4, and 6 h), especially for DHQ100 rather than DHQ40. Docking results explained that quercetin competitively occupies DHQ's binding site or binds to the inhibitor site of P-gp. These results were valuable for improving DHQ absorption.

Keywords

P-gp inhibitors; P-gp substrates; cellular uptakes; flavonoids; molecular docking; taxifolin.

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